SEPSIS BULLETIN 4 January 2019 - Oxford Patient Safety Collaborative
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Here is the latest edition of the Sepsis Bulletin. The bulletin covers the latest information on sepsis and comes out fortnightly. Next edition is due 18 January 2019. Older editions are available as pdfs on the Keeping Up To Date library guide (http://libguides.bodleian.ox.ac.uk/Keeping_up_to_date) Please also pass the bulletin on to other interested people and encourage them to sign up. Anyone can be added to the mailing list. To support you further in keeping up to date, we have a current awareness service, KnowledgeShare. You let us know about the different areas you are interested in (for example lung cancer, leadership, orthopaedics, infection control, patient safety, etc.) and we send out an email fortnightly with any new high‐level reports, studies, guidelines which match. This is a free service. For more information see our guide. To sign up, fill out our form: https://ox.libguides.com/ld.php?content_id=31673730 SEPSIS BULLETIN 4 January 2019 Neonatal, paediatric and maternal sepsis Adult sepsis (cont.) Effects of prebiotics on sepsis, necrotizing enterocolitis, The 2018 Surviving Sepsis Campaign’s Treatment mortality, feeding intolerance, time to full enteral Bundle: When Guidelines Outpace the Evidence feeding, length of hospital stay, and stool frequency in Supporting Their Use preterm infants: a meta‐analysis. Spiegel, R. et al Chi, C. et al Ann Emerg Med. 2018 Aug 30. pii: S0196‐ European journal of clinical nutrition December 19, 0644(18)30607‐3 2018 Although well intentioned, the current sepsis bundles Prebiotics are increasingly recognized as an effective and the potential penalties associated with measure to promote health and prevent adverse health noncompliance lay a heavy weight on ED care absent outcomes in preterm infants. We aimed to evidence that a net benefit will follow. The proposed systematically review the randomized controlled trials Surviving Sepsis Campaign abbreviated bundle (RCTs) in this area. The results showed that the use of heightens the burden by further restricting the time prebiotics with preterm infants is safe and can decrease allotted for the identification and treatment of the incidence of sepsis, mortality, length of hospital patients with suspected sepsis, all without any stay, and time to full enteral feeding but not NEC. evidence of benefit or knowledge of the logistic consequences or cost. A more thoughtful approach to both the identification and management of patients with sepsis is needed, one that engages all
Sepsis prediction during outbreaks at neonatal stakeholders and experts, including the emergency intensive care units through body surface screening for medicine clinicians who treat most patients Gram‐negative bacteria: systematic review and meta‐ hospitalized with sepsis and who will be responsible analysis. for implementing these recommendations. A better strategy will identify more meaningful time stamps, Harder, T. et al focus less on the exact volume of fluid administered, BMC research notes, December 22, 2018, Vol.11(1), and concentrate on identifying the subgroup of septic p.917 patients who will benefit from timely, appropriate care while limiting the diagnostic noise and logistic burdens This systematic review focusses on the prognostic that come with oversensitive screening tools. accuracy of neonatal body surface screening during outbreaks caused by Gram‐negative bacteria for prediction of sepsis. In a previous systematic review we A Comparison of the Quick Sequential (Sepsis‐Related) reported that only limited evidence of very low quality Organ Failure Assessment Score and the National Early exists regarding the predictive value of this screening Warning Score in Non‐ICU Patients With/Without under routine conditions. We aimed to investigate Infection whether this is different in outbreak settings. Extending a previously published systematic review, we show Redfern, O.C. et al here that in contrast to routine settings sensitivity of Critical Care Medicine: December 2018 ‐ Volume 46 ‐ body surface screening for sepsis prediction is very Issue 12 ‐ p 1923–1933 high, while specificity is still insufficient. Surface screening appears to be a useful component of bundles The Sepsis‐3 task force recommended the quick of interventions used during outbreaks, but the Sequential (Sepsis‐Related) Organ Failure Assessment evidence base is still limited. score for identifying patients with suspected infection who are at greater risk of poor outcomes, but many hospitals already use the National Early Warning Score Immunologic biomarkers for diagnostic of early‐onset to identify high‐risk patients, irrespective of diagnosis. neonatal sepsis. We sought to compare the performance of quick Sequential (Sepsis‐Related) Organ Failure Assessment Memar, M.Y. et al and National Early Warning Score in hospitalized, non‐ The journal of maternal‐fetal & neonatal medicine ICU patients with and without an infection. The January 2019, Vol.32(1), pp.143‐153 National Early Warning Score outperforms the quick Sequential (Sepsis‐Related) Organ Failure Assessment Accurate identification of early onset neonatal sepsis score, irrespective of infection status. These findings (EOS) is challenging. Blood culture has been considered suggest that quick Sequential (Sepsis‐Related) Organ as a gold standard method but the identification of EOS Failure Assessment should be re‐evaluated as the is intricate by a high false‐negative results. This review system of choice for identifying non‐ICU patients with provides an overview of biomarkers as indicators for suspected infection who are at greater risk of poor the diagnosis of EOS. There is an affluence of studies outcome. appraising diagnostic indicators in the identification of EOS. Acute‐phase reactants, cytokines, and cell surface antigens have been investigated as indicators for EOS, A Retrospective Review of the Sepsis Definition after but none of them are presently in routine clinical Publication of Sepsis‐3. setting. Despite the promising data for some immunologic biomarkers, present evidence shows that Braun, Derek none of them can constantly diagnose 100% of The American journal of medicine, November 22, infections. IL‐6 is the most potent marker for evaluation 2018 of EOS prognosis. Procalciton (PCT) and C‐reactive protein (CRP) are appropriate indicators for the Two and a half years after the introduction of Sepsis‐3, detection and monitoring of antibiotics therapy. A clinicians continue not to document Sequential Organ panel of sepsis biomarkers along with presently routine Failure Assessment (SOFA) scores. The purpose of this
tests will make easy earlier identification, appropriate review is to determine if the Third International management, and improved outcome may be more Consensus Definitions for Sepsis and Septic Shock efficient than single indicator. (Sepsis‐3) were being utilized in defining sepsis in the clinical setting. There continue to be variations in what standard is accepted by both commercial payers and Screening for colonisation with gentamicin‐resistant the Centers for Medicare and Medicaid (CMS) in Gram‐negative organisms on the neonatal unit: does diagnosing sepsis. Due to Sepsis‐3 criteria not being positive screening predict sepsis? accepted by CMS or the Infectious Disease Society of America, along with it not being able to be Walker, O. et al operationalized for use in the clinical setting, it is Archives of disease in childhood. Fetal and neonatal recommended to continue utilizing systemic edition, January 2019, Vol.104(1), pp.F113‐F114 inflammatory response syndrome criteria plus infection while Sepsis‐3 continues to be evaluated. It At our tertiary‐level neonatal unit, surface swabs have will also allow for some time to study any effect it may been taken weekly to screen for gentamicin‐resistant have on patient outcomes. There is also a need for a GNB. We conducted a retrospective analysis to uniform definition of sepsis. investigate whether colonisation screening in our unit is effective at predicting LOS. Early Post‐Intensive Care Syndrome among Older Adult Sepsis Survivors Receiving Home Care. Severe group A streptococcal infections in mothers and their newborns in London and the South East, 2010– Riegel, B. et al 2016: assessment of risk and audit of public health Journal of the American Geriatrics Society, November management 30, 2018 Leonard, A. et al New or worsened disabilities in functional, cognitive, BJOG : an international journal of obstetrics and or mental health following an intensive care unit (ICU) gynaecology, January 2019, Vol.126(1), pp.44–53. stay are referred to as post‐intensive care syndrome (PICS). PICS has not been described in older adults Are public health guidelines being followed in the receiving home care. Our aim was to examine the management of mothers and their newborns to reduce relationship between length of ICU stay and PICS the risk of iGAS infection? We describe cases of invasive among older adults receiving home care. We expected group A Streptococcus (iGAS) in mothers or neonates that patients in the ICU for 3 days or longer would and assess management according to national demonstrate significantly more disability in all three guidelines, which recommend administering antibiotics domains on follow‐up than those not in the ICU. A to both mother and neonate if either develops iGAS secondary aim was to identify patient characteristics infection within 28 days of birth and investigation of increasing the odds of disability. Older adults receiving clusters in maternity units. iGAS infection remains a home care who develop sepsis and are in an ICU for 3 potential postpartum risk. Prophylaxis among neonates days or longer, are likely to develop new or worsened and storage of isolates from maternity cases can be physical disabilities. Whether these disabilities remain improved. after the early post‐discharge phase requires further study. Genetic polymorphisms and sepsis in premature neonates. Sepsis: developing new alternatives to reduce Esposito, S. et al neuroinflammation and attenuate brain injury. PloS one, 2014, Vol.9(7), p.e101248 Meneses G. et al Identifying single nucleotide polymorphisms (SNPs) in Ann N Y Acad Sci. 2018 Nov 29. the genes involved in sepsis may help to clarify the
pathophysiology of neonatal sepsis. The aim of this Sepsis occurs when a systemic infection induces an study was to evaluate the relationships between sepsis uncontrolled inflammatory response that results in in pre‐term neonates and genes potentially involved in generalized organ dysfunction. The exacerbated the response to invasion by infectious agents. The peripheral inflammation can induce, in turn, results show that genetic variability seems to play a neuroinflammation which may result in severe role in sepsis in pre‐term neonates by influencing impairment of the central nervous system (CNS). susceptibility to and the severity of the disease, as well Indeed, the ensuing blood‐brain barrier disruption as the risk of having disease due to specific pathogens. associated with sepsis promotes glial activation and starts a storm of proinflammatory cytokines in the CNS that leads to brain dysfunction in sepsis survivors. Earlier and more targeted treatment of neonatal sepsis. Endotoxic shock induced in mice by peripheral injection of lipopolysaccharides closely resembles the Özenci, V. et al peripheral and central inflammation observed in Acta paediatrica (Oslo, Norway : 1992), January 2019, sepsis. In this review, we provide an overview of the Vol.108(1), pp.169‐170 neuroinflammatory features in sepsis and of recent progress toward the development of new anti‐ Neonatal sepsis occurs in 1–2 of the 1000 live born neuroinflammatory therapies seeking to reduce neonates and accounts for 3‐5% of deaths in term and mortality and morbidity in sepsis survivors. more than 30% in extremely preterm infants. These mortality rates due to neonatal infections are unacceptably high. Immediate and targeted antibiotic Autophagy and skeletal muscles in sepsis. treatment is crucial in order to improve survival in this vulnerable population. Pilot study. Mofarrahi, M. et al PloS one, 2012, Vol.7(10), p.e47265 Which biomarkers reveal neonatal sepsis? Mitochondrial injury develops in skeletal muscles during the course of severe sepsis. Autophagy is a Wang K. et al protein and organelle recycling pathway which PLoS One. 2013 Dec 18;8(12):e82700. functions to degrade or recycle unnecessary, redundant, or inefficient cellular components. No We address the identification of optimal biomarkers for information is available regarding the degree of sepsis‐ the rapid diagnosis of neonatal sepsis. We employ both induced mitochondrial injury and autophagy in the canonical correlation analysis (CCA) and sparse support ventilatory and locomotor muscles. This study tests vector machine (SSVM) classifiers to select the best the hypotheses that the locomotor muscles are more subset of biomarkers from a large hematological data prone to sepsis‐induced mitochondrial injury, set collected from infants with suspected sepsis from depressed biogenesis and autophagy induction Yale‐New Haven Hospital's Neonatal Intensive Care compared with the ventilatory muscles. We conclude Unit (NICU). CCA is used to select sets of biomarkers of that locomotor muscles are more prone to sepsis‐ increasing size that are most highly correlated with induced mitochondrial injury, decreased biogenesis infection. The effectiveness of these biomarkers is then and increased autophagy compared with the validated by constructing a sparse support vector ventilatory muscles and that autophagy in skeletal machine diagnostic classifier. We find that the muscles during sepsis is regulated in part through the following set of five biomarkers capture the essential NFκB transcription factor. diagnostic information (in order of importance): Bands, Platelets, neutrophil CD64, White Blood Cells, and Segs. Further, the diagnostic performance of the optimal set Interleukin 38 Protects Against Lethal Sepsis. of biomarkers is significantly higher than that of isolated individual biomarkers. These results suggest an Xu, F. et al enhanced sepsis scoring system for neonatal sepsis that The Journal of infectious diseases, August 24, 2018, includes these five biomarkers. We demonstrate the Vol.218(7), pp.1175‐1184 robustness of our analysis by comp
Interleukin 38 (IL‐38) is the most recently characterized cytokine of the interleukin 1 family. Mupirocin for Staphylococcus aureus Decolonization of However, its role in sepsis remains unknown. Our Infants in Neonatal Intensive Care Units. findings suggest that IL‐38 attenuates sepsis by Kotloff, K.L.1et al decreasing inflammation and increasing bacterial clearance, thus providing a novel tool for antisepsis Pediatrics. 2019 Jan;143(1). pii: e20181565. therapy. Staphylococcus aureus (SA) is the second leading cause of late‐onset sepsis among infants in the NICU. Because colonization of nasal mucosa and/or skin frequently Sepsis‐The "Gift" That Keeps on Giving, Regardless of precedes invasive infection, decolonization strategies, Age. such as mupirocin application, have been attempted to Simpson, S.Q. prevent clinical infection, but data supporting this approach in infants are limited. We conducted a phase Critical care medicine, August 2018, Vol.46(8), 2 multicenter, open‐label, randomized trial to assess pp.1378‐1380 the safety and efficacy of intranasal plus topical There is little doubt that sepsis is an affliction mupirocin in eradicating SA colonization in critically ill associated with aging. Editorial infants. Application of mupirocin to multiple body sites was safe and efficacious in eradicating SA carriage among infants in the NICU; however, after 2 to 3 weeks, many infants who remained hospitalized A minimal set of physiomarkers in continuous high became recolonized. frequency data streams predict adult sepsis onset earlier van Wyk, F. et al Management of Neonates Born at ≥35 0/7 Weeks’ Gestation With Suspected or Proven Early‐Onset International Journal of Medical Informatics, Bacterial Sepsis 02/2019, Vol.122, C, pp.55‐62 Puopolo, K. et al Sepsis is a life‐threatening condition with high mortality rates and expensive treatment costs. To Pediatrics, Dec 2018, Vol.142(6), p.1 improve short‐ and long‐term outcomes, it is critical to detect at‐risk sepsis patients at an early stage. A The incidence of neonatal early‐onset sepsis (EOS) has random forest classifier was trained to discriminate declined substantially over the last 2 decades, primarily between sepsis and non‐sepsis patients. The use of because of the implementation of evidence‐based machine learning algorithms on continuous streams of intrapartum antimicrobial therapy. However, EOS physiological data can allow for early identification of remains a serious and potentially fatal illness. at‐risk patients in real‐time with high accuracy. Laboratory tests alone are neither sensitive nor specific enough to guide EOS management decisions. Maternal and infant clinical characteristics can help identify newborn infants who are at risk and guide the Exploring the Pathways Revealed by International administration of empirical antibiotic therapy. The Sepsis Benchmarking. incidence of EOS, the prevalence and implications of Walkey, A.J. established risk factors, the predictive value of commonly used laboratory tests, and the uncertainties Critical care medicine, January 2019, Vol.47(1), in the risk/benefit balance of antibiotic exposures all pp.135‐137 vary significantly with gestational age at birth. Editorial Sepsis programme successes are responsible for the Adult sepsis increased detection of bacteraemia.
Association of Corticosteroid Treatment With Simmons, M D et al Outcomes in Adult Patients With Sepsis: A Systematic The Journal of hospital infection, January 2019, Review and Meta‐analysis. Vol.101(1), pp.93‐99 Fang, F. et al Escherichia coli bacteraemia reduction targets are JAMA internal medicine, December 21, 2018 challenging but, in West Wales, this was the key infection surrogate measure set by the local health Although corticosteroids are widely used for adults board in 2013, prior to the introduction of a Welsh with sepsis, both the overall benefit and potential risks Government target. The initial plateau of cases was remain unclear. We conducted a systematic review and not maintained and prompted this review. Success in meta‐analysis of the efficacy and safety of one area (sepsis management) conflicts with 'failure' in corticosteroids in patients with sepsis. The findings reducing E. coli bacteraemia. It is argued that targets suggest that administration of corticosteroids is need to be considered carefully in the light of all associated with reduced 28‐day mortality compared available with placebo use or standard supportive care. More research is needed to associate personalized medicine with the corticosteroid treatment to select suitable Sepsis: Early Recognition and Optimized Treatment. patients who are more likely to show a benefit. Kim, H.I. et al Tuberculosis and respiratory diseases, January 2019 Identification of subclasses of sepsis that showed Vol.82(1), pp.6‐14 different clinical outcomes and responses to amount of fluid resuscitation: a latent profile analysis. Sepsis is a life‐threatening condition caused by infection and represents a substantial global health Zhang, Z. et al burden. Recent epidemiological studies showed that Critical care (London, England), December 18, 2018, sepsis mortality rates have decreased, but that the Vol.22(1), p.347 incidence has continued to increase. Although a mortality benefit from early‐goal directed therapy Sepsis is a heterogeneous disease and identification of (EGDT) in patients with severe sepsis or septic shock its subclasses may facilitate and optimize clinical was reported in 2001, three subsequent multicenter management. This study aimed to identify subclasses of randomized studies showed no benefits of EGDT sepsis and its responses to different amounts of fluid versus usual care. Nonetheless, the early resuscitation. The study identified four subphenotypes administration of antibiotics and intravenous fluids is of sepsis, which showed different mortality outcomes considered crucial for the treatment of sepsis. In 2016, and responses to fluid resuscitation. Prospective trials new sepsis definitions (Sepsis‐3) were issued, in which are needed to validate our findings. organ failure was emphasized and use of the terms “systemic inflammatory response syndrome” and “severe sepsis” was discouraged. However, early Effect of cytomegalovirus reactivation on the time detection of sepsis with timely, appropriate course of systemic host response biomarkers in interventions increases the likelihood of survival for previously immunocompetent critically ill patients with patients with sepsis. Also, performance improvement sepsis: a matched cohort study. programs have been associated with a significant van de Groep, K. et al increase in compliance with the sepsis bundles and a reduction in mortality. To improve sepsis management Critical care (London, England), December 18, 2018, and reduce its burden, in 2017, the World Health Vol.22(1), p.348 Assembly and World Health Organization adopted a Cytomegalovirus (CMV) reactivation in previously resolution that urged governments and healthcare immunocompetent critically ill patients is associated workers to implement appropriate measures to with increased mortality, which has been hypothesized address sepsis. Sepsis should be considered a medical to result from virus‐induced immunomodulation. Therefore, we studied the effects of CMV reactivation
on the temporal course of host response biomarkers in emergency, and increasing the level of awareness of patients with sepsis. CMV reactivation was not sepsis is essential. independently associated with changes in the temporal trends of host response biomarkers in comparison with non‐reactivating patients. Therefore, these markers Low D‐dimer levels in sepsis: Good or bad? should not be used as surrogate clinical endpoints for interventional studies evaluating anti‐CMV therapy. Semeraro, F. et al Thrombosis research, Vol.174, pp.13‐15 December 5, 2018 APRIL and sTACI could be predictors of multiorgan dysfunction syndrome in sepsis. DIC is a serious complication of sepsis and increases the risk of death. D‐dimer (DD) is the most used fibrin‐ Lendak, D.F. et al related marker for DIC diagnosis. However, DD levels depend on both coagulation and fibrinolysis. Patients Virulence, December 31, 2018, Vol.9(1), pp.946‐953 with severe sepsis and normal DD were shown to have Although the role of B cells in sepsis immunoregulation the highest mortality. Allegedly, normal DD in sepsis has become an interesting topic, there is lack of data masks a DIC form with strong fibrinolysis inhibition. on the role of B cell function regulators in prediction of Letter multiorgan dysfunction syndrome (MODS). The aim of this study was to evaluate the prognostic value of A Proliferation Inducing Ligand (APRIL) and soluble Effects of antiplatelet therapy on the mortality rate of Transmembrane Activator and CAML Interactor Protein patients with sepsis: A meta‐analysis. (sTACI), the main B cell function regulators, in prediction of MODS development within the first 48h Ouyang, Y. et al after admission to intensive care unit, among septic Journal of critical care, Vol.50, pp.162‐168 December patients. Elevated level of sTACI could be the alarm for 5, 2018 the increased B cell apoptosis and development of immune paralysis. Including these biomarkers into Abnormal platelet activation plays an important role in predictive scores specific for septic patients may the development of sepsis. The effect of antiplatelet potentially improve their sensitivity and specificity. drugs on the outcome of patients with sepsis remains Measurement of their concentrations dynamics could unclear. This meta‐analysis aimed to determine the contribute to better assessment of sepsis evolution and effect of antiplatelet drugs on the prognosis of timely introduction of immunomodulatory therapy. patients with sepsis. Antiplatelet drugs, particularly aspirin, could be used to effectively reduce mortality in patients with sepsis. Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Doppler‐defined pulmonary hypertension in sepsis and Outcome in Sepsis and Septic Shock‐1 (AdrenOSS‐1) septic shock. study. Vallabhajosyula, S. et al Mebazaa, A. et al Journal of critical care, December 8, 2018, Vol.50, Critical care (London, England), December 21, 2018, pp.201‐206 Vol.22(1), p.354 The association of pulmonary hypertension (PH) in Adrenomedullin (ADM) regulates vascular tone and patients with sepsis is lesser understood. In patients endothelial permeability during sepsis. Levels of with sepsis and septic shock, PH is common and is circulating biologically active ADM (bio‐ADM) show an noted to be associated with higher short and long‐ inverse relationship with blood pressure and a direct term mortality. Further studies are needed to relationship with vasopressor requirement. In the understand the mechanisms by which PH is associated present prospective observational multinational with outcomes.
Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS‐1) study, we assessed relationships An electronic warning system helps reduce the time to between circulating bio‐ADM during the initial diagnosis of sepsis. intensive care unit (ICU) stay and short‐term outcome in order to eventually design a biomarker‐guided Westphal, G. A. et al randomized controlled trial. AdrenOSS‐1 shows that early levels and rapid changes in bio‐ADM estimate Revista Brasileira de terapia intensiva, December 13, short‐term outcome in sepsis and septic shock. These 2018 data are the backbone of the design of the biomarker‐ To describe the improvements of an early warning guided AdrenOSS‐2 trial. system for the identification of septic patients on the time to diagnosis, antibiotic delivery, and mortality. This was an observational cohort study that describes the successive improvements made over a period of 10 years using an early warning system to detect sepsis, including systematic active manual surveillance, electronic alerts via a telephonist, and alerts sent directly to the mobile devices of nurses. For all periods, after an alert was triggered, early treatment was instituted according to the institutional sepsis guidelines. Electronic systems help reduce the triage‐ to‐diagnosis time and diagnosis‐to‐antibiotic time in patients with sepsis. Need further help? The outreach team at the Bodleian Health Care Libraries is here to support the information needs of all OUH Trust staff. We’re happy to help you with literature searches, search skills training and advice, keeping you up to date, and general references enquiries. Contact us: 01865 221936 hcl‐firstname.lastname@example.org www.bodleian.ox.ac.uk/nhs Register for OpenAthens to access e‐resources: https://openathens.nice.org.uk/ Bulletin content based partly on CASH (Current Awareness Service for Health) here To subscribe/unsubscribe from this bulletin please email email@example.com or reply to this email. Please see our privacy notice https://libguides.bodleian.ox.ac.uk/Keeping_up_to_date/privacynotice
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